1. Field of the Invention
This invention pertains generally to aerosol generating devices, and more particularly to inhalers that may be used to dispense liquid or powder medication in short bursts of aerosol.
2. Description of the Background Art
Some medicines cannot withstand the environment of the digestive tract and must be delivered to the bloodstream of the patient intravenously or by some other method. One effective means for delivery of such medications to the blood stream is through the membranes and air passageways of the lung.
Inhalers of various types have been widely used for inhalation delivery of aerosols containing medication or other constituents to the conductive airways of the lung and the gas exchange regions of the deep lung. Aerosols are relatively stable suspensions of finely divided droplets or solid particles in a gaseous medium. When inhaled, aerosol particles may be deposited by contact upon the various surfaces of the respiratory tract leading to the absorption of the particles through the membranes of the lung into the blood stream to provide the desired therapeutic action, or planned diagnostic behavior depending on the particular properties of the particles.
Because of the high permeability of the membranes of the lung and the copious flow of blood through the lung, medications deposited in the lung can readily enter the blood stream for delivery throughout the body. This may also allow for the use of lower initial doses than would normally be required to be taken orally to achieve the desired concentration of medication in the blood. Other medications can directly influence the airway epithelium and effect responses via various airway receptors. Still other types of aerosol particles deposited in the lung can act as tracers of airflow or indicators of lung responses and can otherwise be a valuable diagnostic tool. Properly generated and formulated aerosols can therefore be helpful in medical treatment. Inhalable aerosol particles capable of deposition within the lung are typically those with an aerodynamic equivalent diameter of between 1 and 5 micrometers.
Early attempts at producing an inhalation medical treatment include the use of atomizers. Atomizers are typically equipped with reservoirs, nozzles, and bulbs. Upon squeezing the bulb, liquid medication, which is placed within the reservoir, is drawn from the reservoir and sprayed by the nozzle for inhalation by the patient. However, the particle size produced by atomizers is too large for effective deposition in the lungs, although variants of the technique are still used for deposition of topical medication into the nasal cavity and associated tissues. A further disadvantage of atomizers is that they are unable to deliver a consistent dose due to discrepancies in user technique and the duration of each burst. Accordingly, atomizers are appropriate for delivery of medication to the sinus cavity, where the larger aerosol particle size is more effective for deposition but inappropriate for deposition in the deep lung.
Inhalers known in the art employ several techniques to achieve effective aerosolization of medicines for deposition in the lung. An inhaler produces a burst of aerosol consisting of fine particles intended for inhalation by a patient with a single breath. Inhalers are popular aerosol delivery devices because they are generally portable and are convenient to use. The particle size of the aerosol emitted from a typical inhaler is required to be considerably smaller than a conventional spray atomizer to ensure the appropriate deposition within the lungs.
Commonly, inhalers are pre-packaged containers containing a mixture of medication to be aerosolized and a low saturation pressure vapor or gas, such as chlorofluorocarbons (CFCs), which are used as a propellant. The canister carrying the mixture of the medication and the propellant is equipped with a valve. When the valve is actuated, the inhaler dispenses a set amount of liquid and medication through a nozzle, creating a spray. Upon release into the atmosphere, the low saturation pressure propellant is able to evaporate quickly leaving small aerosol particles of medication that are suitable for immediate inhalation. One disadvantage to this approach is that the propellant and the medication must be mixed for a significant period of time prior to inhalation by the patient, making them unsuitable for many medications. Furthermore, the pre-mixing of the medication and the propellant requires a different approach to gain regulatory approval, necessitating significant development time and capital, thereby significantly increasing the ultimate cost to the patient over the cost of liquid formulations of same medication. Furthermore, to prevent agglomeration of the medication within the canister, surfactants are also added to the formulation, which often leave an undesirable taste in the mouth of the patient after inhalation. Lastly, this approach is generally unsuitable for medications requiring large quantities of medication to achieve efficacious results.
Another inhaler strategy that is being employed with greater frequency is the aerosolization of dry medicament powders. Medicinal powders are prepared in advance and placed in a reservoir within the inhaler, or within blister pouches. Blister pouches have the advantage of being able to better preserve the powder from contamination and moisture. When the patient is ready for a dose of medication, they either access the reservoir to dispense an appropriate amount of powdered medication, or puncture a blister pouch containing the powder medicament.
Aerosolization of powders is typically achieved by the gas flow produced by the inhalation of the patient. However, the aerosolization of medicinal powders is plagued by problems of moisture contamination and the inconsistencies in inhalation effort by the patient from dose to dose. Furthermore, powder formulations are often as expensive to develop as pre-mixed propellants and may require complex, sophisticated and expensive manufacturing processes in their production. In addition, many medications are not effective after reformulation as a powder. Finally, powder aerosolization may be ineffective due to the appearance of an electric charge build up on the individual powder particles causing particles to attach to other particles or to the delivery device. Recent studies using inhaled powder medications have indicated that problems of pulmonary fibrosis may exist when treating chronic conditions with inhaled powder medication.
A third inhaler strategy employs ultrasonic energy to aerosolize bursts of liquid medication. These devices require precise electronic valves and associated electronic circuitry, making them expensive to manufacture and prone to malfunction. Additionally, the particle size of the aerosol produced by these devices is often too large for optimal deposition in the lung. Large and inconsistent aerosol particle size production by the inhaler results in an inconsistent and inefficient delivery of the medication to the lung.
Additionally, ultrasonic inhalers using piezo-electric crystals to create aerosolization of the medicine are often not suitable for delivering proteins, peptides and antibodies and the like because of the damage and loss of biological activity that occurs with ultrasound. Other medicines have required expensive reformulizations in order to be delivered by the ultrasonic aerosolization method. Lastly, ultrasonic inhaler technologies have been shown to have difficulties in delivering concentrated medication, making them suitable for potent medications only, and unsuitable for the delivery of medication requiring large quantities of medication to be efficacious.
Therefore, a need exists for a technology which can deliver aerosol bursts of liquid medication at a particle size that is appropriate for lung deposition which is inexpensive for the patient, produces consistent output, uses a formulation which is inexpensive to develop and produce, that is reliable, that is easy to use, which does not require the mixing of medication and propellant until the moment of aerosolization, and which can deliver large quantities of medication when needed. The present invention satisfies this need, as well as others and has the further advantages of providing superior aerosol quality, and being lightweight and portable.